Preliminary Study On Hdac4 In Osteoblast Differentiation

Recently, more and more studies have focused on the treatment of bone diseases such as osteoporosis. People developed various therapies through inhibiting bone resorption or promoting bone formation. To consider the possibility of promoting bone formation, many people are now analyzing the transcription factors essential for bone development, such as Runx2 and Osterix, and clarifying the relationships between the transcription factors and their related factors. Histone deacetylases are enzymes (HDACs) that can regulate the activity of transcription factors and affect bone development. HDAC4 is a member of the A subclass of type II HDAC family and is a protein shuttling from nuclear and cytoplasm. Parathyroid hormone (PTH) is a bone anabolic hormone, which can regulate bone mass through affecting bone formation and bone resorption.In this thesis, we performed Western blot and immunofluorescence, RT-PCR and alkaline-phosphatase activity staining experiments, Here, we found PTH was able to induce HDAC4 shutting from cytoplasm to nucleus. This enabled us to study on the relationships between Runx2, Osterix and HDAC4 more conveniently in the future, thereby contributing to the study on mechanisms of bone development and treatment of osteoporosis and providing a more in-depth theoretical basis. This thesis proved that under normal conditions, PTH can make HDAC4 shuttle from cytoplasm to nucleus in C3H10T1/2 mesenchymal stem cells. We also investigated whether HDAC4 influence activities of Runx2 and Osterix. By detecting the mRNA level of bone marker genes and alkaline phosphatase activities, we found the HDAC4 might inhibit Osterix directed osteoblast differentiation probably through an indirect way.